Martha Zewdie

Objectives Immunogenicity of IndoVac (BioFarma), a domestically manufactured SARS-CoV-2 protein subunit ancestral-strain vaccine, has not been well-studied. We evaluated fifth-dose IndoVac, following third- and fourth-dose mRNA vaccination, among Indonesian healthcare workers (HCWs). Methods Between August 2023 and January 2025, we measured anti-S-RBD IgG titres, neutralising antibody (nAb) titres against six Omicron-subvariants, and IFN-γ T-cell responses, before and 28 days after vaccine dose 3-5 in 30 HCWs. Results Anti-S-RBD IgG and nAb titres increased after third-dose mRNA vaccine (34.7-fold and 28.4–61.9-fold, respectively) and increased further after fourth-dose mRNA vaccine (4.2-fold and 4.8–6.8-fold, respectively), whereas fifth-dose IndoVac did not further improve antibody titres (1.3-fold and 1.9–4.1-fold decline, respectively). nAb titres against XBB-subvariants were consistently lower than against ancestral-strain. IFN-γ T-cell responses were detectable in most individuals after respective third, fourth, and fifth doses, both against ancestral-strain (91.7%, 100%, and 90.0%) and Omicron BA 2.86 (66.7%, 100%, and 100%). T-cell responses increased 3.6-fold after third-dose and remained stable thereafter. Conclusions Compared to immunogenic mRNA booster, IndoVac did not boost humoral or cellular immune responses against ancestral and Omicron-subvariants. These findings support efforts to advance domestic vaccine manufacturing capacity in LMICs, to ensure vaccine formulations can effectively target emerging SARS-CoV-2 variants.

Few studies in sub‐Saharan Africa evaluate Institutional Review Boards (IRBs) capacity. The study aims to explore the composition of IRBs, training, and challenges experienced in the ethics review processes by members of research institutions and universities in Addis Ababa, Ethiopia. Our findings indicate that most IRBs members were trained on research ethics and good clinical practice. However, majority perceived the trainings as basic. IRB members faced several challenges including: investigators wanting rapid review; time pressure; investigators not following checklists; limited expertise in reviewing clinical trials, studies on genetics, and traditional medicine; lack of IRB offices for administrative work; competing tasks; limited staffing and the lack of a standardized review system. There is need for advanced training on research ethics to meet the evolving research needs. In addition, investments in IRBs are needed in terms of funding, and physical and human resources in Addis Ababa and Ethiopia in general.

H1/IC31® is a tuberculosis (TB) subunit vaccine candidate consisting of the fusion protein of Ag85B and ESAT-6 (H1) formulated with the IC31® adjuvant. Previous trials have reported on the H1/IC31® vaccine in M. tuberculosis (Mtb)-naïve, BCG-vaccinated and previously Mtb-infected individuals. In this trial, conducted between December 2008 and April 2010, the safety and immunogenicity of H1/IC31® was assessed in participants living in Ethiopia – a highly TB-endemic area. Healthy male participants aged 18–25 years were recruited into four groups. Participants in group 1 (N = 12) and group 2 (N = 12) were Tuberculin Skin Test (TST) negative and QuantiFERON-TB Gold in-tube test (QFT) negative (Mtb-naïve groups), participants in group 3 (N = 3) were TST positive and QFT negative (BCG group), and participants in group 4 (N = 12) were both TST and QFT positive (Mtb-infected group). H1 vaccine alone (group 1) or H1 formulated with the adjuvant IC31® (groups 2, 3 and 4) was administered intramuscularly on day 0 and day 56. Safety and immunogenicity parameters were evaluated for up to 32 weeks after day 0. The H1/IC31®vaccine was safe and generally well tolerated. There was little difference among the four groups, with a tendency towards a higher incidence of adverse events in Mtb-infected compared to Mtb-naïve participants. Two serious adverse events were reported in the Mtb-infected group where a relationship to the vaccine could not be excluded. In both cases the participants recovered without sequelae within 72 h. Immunogenicity assays, evaluated in the 29 participants who received both vaccinations, showed a stronger response to TB antigens in the Mtb-naïve group vaccinated with the adjuvant. The trial confirmed the need for an adjuvant for the vaccine to be immunogenic and highlighted the importance of early phase testing of a novel TB vaccine candidate in TB-endemic areas. ClinicalTrials.gov, ID: NCT01049282. Retrospectively registered on 14 January 2010.

M. tuberculosis remains one of the world’s deadliest pathogens in part because of its ability to establish persistent, latent infections, which can later reactivate to cause disease. In regions of the globe where disease is endemic, as much as 50% of the population is thought to be latently infected, complicating diagnosis and tuberculosis control. The tools most commonly used for diagnosis of latent M. tuberculosis infection are the tuberculin skin test and the newer interferon-gamma release assays, both of which rely on an antigen-specific memory response as an indicator of infection. It is clear that the two tests, do not always give concordant results, but the factors leading to this are only partially understood. In this study we examined 245 healthy school children aged from 12 to 20 years from Addis Ababa, a tuberculosis-endemic region, characterised them with regard to response in the tuberculin skin test and QuantIFERON™ test and assessed factors that might contribute to discordant responses. Although concordance between the tests was generally fair (90% concordance), there was a subset of children who had a positive QuantIFERON™ result but a negative tuberculin skin test. After analysis of multiple parameters the data suggest that discordance was most strongly associated with the presence of parasites in the stool. Parasitic gut infections are frequent in most regions where M. tuberculosis is endemic. This study, while preliminary, suggests that the tuberculin skin test should be interpreted with caution where this may be the case.

Despite major public health initiatives and the existence of efficacious treatment regimes, tuberculosis (TB) remains a threat, particularly in resource-limited settings. A significant part of the problem is the difficulty of rapidly identifying infected individuals, and as a result, there has been renewed interest in developing better diagnostics for infection or disease caused by Mycobacterium tuberculosis. Many of the existing tools, however, have limitations such as poor sensitivity or specificity, or the need for well-equipped laboratories to function effectively. Serodiagnostic approaches in particular have long drawn attention, due to their potential utility in large field studies, particularly in resource-poor settings. Unfortunately none of the serodiagnostic approaches have so far proven useful under field conditions.

One third of the world’s population is thought to have latent tuberculosis infection (LTBI) with the potential for subsequent reactivation of disease. To better characterize this important population, studies comparing Tuberculin Skin Test (TST) and the new interferon-γ release assays including QuantiFERON®-TB Gold In-Tube (QFT-GIT) have been conducted in different parts of the world, but most of these have been in countries with a low incidence of tuberculosis (TB). The aim of this study was therefore to evaluate the use of QFT-GIT assay as compared with TST in the diagnosis of LTBI in Ethiopia, a country with a high burden of TB and routine BCG vaccination at birth.